ArticleOncogene2007
Transcriptional upregulation of p57 (Kip2) by the cyclin-dependent kinase inhibitor BMS-387032 is E2F dependent and serves as a negative feedback loop limiting cytotoxicity.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 32 citations in OpenAlex.
- CIP/KIP and INK4 families as hostages of oncogenic signaling.Cell division · 2024Review
- CDKN1C as a prognostic biomarker correlated with immune infiltrates and therapeutic responses in breast cancer patients.Journal of cellular and molecular medicine · 2021Article
- Functional Versatility of the CDK Inhibitor p57Frontiers in cell and developmental biology · 2020Review
- Article
- Knockdown ofOncology letters · 2018Article
- Maternal-fetal conflict, genomic imprinting and mammalian vulnerabilities to cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015Review
- Endoreplication.Cold Spring Harbor perspectives in biology · 2013Review
- HIF-1α deletion partially rescues defects of hematopoietic stem cell quiescence caused by Cited2 deficiency.Blood · 2012Article
- The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer.British journal of cancer · 2012Article
- Increased expression of bcl11b leads to chemoresistance accompanied by G1 accumulation.PloS one · 2010Article
- CDKN1C negatively regulates RNA polymerase II C-terminal domain phosphorylation in an E2F1-dependent manner.The Journal of biological chemistry · 2010Article
- A small-molecule E2F inhibitor blocks growth in a melanoma culture model.Cancer research · 2008Article
- RhoBTB2 (DBC2) is a mitotic E2F1 target gene with a novel role in apoptosis.The Journal of biological chemistry · 2008Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
In spite of the fact that cyclin-dependent kinase (cdk) inhibiting drugs are potent transcriptional repressors, we discover that p57 (Kip2, CDKN1C) transcription is significantly upregulated by three small molecule cdk inhibitors, including BMS-387032. Treatment of MDA-MB-231 breast cancer cells with BMS-387032 led to a stabilization of the E2F1 protein that was accompanied by significant increases in the p57 mRNA and protein. This increase did not occur in an E2F1-deficient cell line. An E2F1-estrogen receptor fusion protein activated the endogenous p57 promoter in response to hydroxytamoxifen treatment in the presence of cycloheximide. Luciferase constructs driven by the p57 promoter verified that upregulation of p57 mRNA by BMS-387032 is transcriptional and dependent on E2F-binding sites in the promoter. Expression of exogenous p57 significantly decreased the fraction of cells in S phase. Furthermore, p57-deficient MDA-MB-231 cell lines were significantly more sensitive to BMS-387032-induced apoptosis than controls. The results presented in this manuscript demonstrate that small molecule cdk inhibitors transcriptionally activate p57 dependent upon E2F1 and that this activation in turn serves to limit E2F1's death-inducing activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.